The increased exposure to ultraviolet (UV) radiation due to ozone depletion is one of the most serious global health problems. The UV exposure is known to cause skin carcinoma, cataract and deteriorated immune function, but for countries like Japan, the magnitude of health effects of UV radiation is yet to be elucidated. The International Workshop on the Health Effects of Ultraviolet Radiation was held in Tokyo, Japan, on February 17-19, 1999, in attempts to visualize the size of this problem and to identify better solutions. Through this workshop, several lines of scientific evidence were provided, which clearly show that the risk of cataract and skin cancer among people living in Japan increases with the increasing level of sun exposure. We must seek, therefore, the extent to which the UV exposure of given intensity causes adverse health effects in Japanese population. Through the workshop, the importance of preventive measure was confirmed. The scientific basis of prevention is, of course, the knowledge of dose-response relationship and the current exposure status in Japanese population. It is hoped that the communications between researchers in Japan and other countries are strengthened through this workshop. J Epidemiol, 1999; 9 : S1-S4.

Skin cancer is the most commonly occurring cancer in humans. Solar keratoses are related benign tumours that are at least ten times commoner than skin cancers and photoageing of the skin is still more common. Descriptive studies show that incidence rates of the main types of skin cancer, basal cell carcinoma, squamous cell carcinoma and melanoma are maximal in populations in which ambient sun exposure is high and skin (epidermal) transmission of solar radiation is high, suggesting strong associations with sun exposure. Analytic epidemiological studies confirm that exposure to the UV component of sunlight is the major environmental determinant of skin cancers and associated skin conditions and evidence of a causal association between cumulative sun exposure and SCC, solar keratoses and photodamage is relatively straightforward. Results for BCC and melanoma are complicated by several factors including the existence of subgroups of these diseases which do not appear to be caused by sun exposure yet have been included in most aetiological studies to date. Complementary to epidemiological data is the molecular evidence of ultraviolet (UV) mechanisms of carcinogenesis such as UV-specific mutations in the DNA of tumour suppressor genes in skin tumours. With increased UV irradiation resulting from thinning of the ozone layer, skin cancer incidence rates have been predicted to increase in the future unless, as is hoped, human behaviour to reduce sun exposure can offset these predicted rises. J Epidemiol, 1999 ; 9 : S7-S13.

An examination of the occurrence of skin cancers and precancerous lesions among residents of Kasai City (34-56' N) since 1992, and of le-island (25&N 10' N) since 1993, has been conducted to characterize the prevalence and incidence of skin cancers in Japanese people and to evaluate risk and preventive factors. The mean prevalence of actinic keratosis (AK) in residents of Kasai City and le-island was 203.33 and 756.26, respectively, indicating that twice the dose of UVB radiation causes a 3-4 fold higher incidence of AK, although life styles, including types of occupations, differ in these two locations. Working outdoors, having skin type I and/or a history of severe sunburns during childhood were found to be important risk factors, while the use of cosmetics after 20 years of age was a protective factor, for AK and possibly for skin cancers. Further, sunscreen use among males over 60 years of age in Kasai City from 1994 through 1998 suggested that sunscreen use may reduce AK development in older people. Four and 12 cases of skin cancers were found in residents of Kasai City (from 1992 to 1997) and on le-island (from 1993 to 1998), respectively. These numbers are too small to establish the prevalence of skin cancer in Japanese, but indicate that people living in areas of higher ambient solar radiation have a higher incidence of skin cancer. This epidemiological study strongly indicates that sun protection is the major modality to reduce sun-induced cutaneous tumors in Japanese. J Epidemiol, 1999 ; 9 : S14-S21.

An examination of the occurrence of skin cancers and precancerous lesions among residents of Kasai City (34-56' N) since 1992, and of le-island (25&N 10' N) since 1993, has been conducted to characterize the prevalence and incidence of skin cancers in Japanese people and to evaluate risk and preventive factors. The mean prevalence of actinic keratosis (AK) in residents of Kasai City and le-island was 203.33 and 756.26, respectively, indicating that twice the dose of UVB radiation causes a 3-4 fold higher incidence of AK, although life styles, including types of occupations, differ in these two locations. Working outdoors, having skin type I and/or a history of severe sunburns during childhood were found to be important risk factors, while the use of cosmetics after 20 years of age was a protective factor, for AK and possibly for skin cancers. Further, sunscreen use among males over 60 years of age in Kasai City from 1994 through 1998 suggested that sunscreen use may reduce AK development in older people. Four and 12 cases of skin cancers were found in residents of Kasai City (from 1992 to 1997) and on le-island (from 1993 to 1998), respectively. These numbers are too small to establish the prevalence of skin cancer in Japanese, but indicate that people living in areas of higher ambient solar radiation have a higher incidence of skin cancer. This epidemiological study strongly indicates that sun protection is the major modality to reduce sun-induced cutaneous tumors in Japanese. J Epidemiol, 1999 ; 9 : S14-S21.

Cataract epidemiological surveys applying objective judgement through lens images in the climatically different places of Noto and Amami, Japan, Singapore and Reykjavik, Iceland yielded several significant results about the influence of solar UV. 1) The percentage of transparent and of lens opacification was significantly higher in the Reykjavik subjects than in the Singaporeans. 2) The percentages including early changes were higher in Amami and Singapore than in Noto and Reykjavik. 3) Progressed lens opacification was highest in Singapore. While the main type of lens opacification was cortical in Noto and Reykjavik, that of Singapore was nuclear. 4) A significant correlation between cortical opacification and the history of time spent outdoors was noticed. The UV risk for formation and/or progression of cortical opacification should be acceptable from the epidemiological standpoint. J Epidemiol, 1999; 9 : S33-S38.

UV irradiation has the potential to induce the development of lens opacities. This has been demonstrated since long with animal experiments. Unfortunately these animal cataracts did not explain or elucidate the epidemiological observation that the frequency of human cataracts such as the so called senile cataract is remarkably higher in regions with increased cosmic UV irradiation or in the population being in close professional contact with UV-irradiation. The main problem was that the type of UV induced animal cataracts differs remarkably with respect to onset, localization of the opacity, size and its timely progression from the cataract classes observed in human. The research of the last 10 years comes to the conclusion that beside the direct (acute) damage as seen in animal studies due to high UV dosageswe have to realize a synor co-cataractogenic potential of UV irradiation even below the threshold dose which is able to accumulate in the lens and to initiate together with other risk factors (chronic damage) the opacification of the lens. The mechanism for the animal cataract and the human cataract (with an UV risk participation) are different. The epidemiological research about cataract frequency in different regions of the world have to take into account that UV irradiation -even below a threshold dose is a possible risk among the multifactorial pathogenesis of human cataract. J Epidemiol, 1999; 9 : S39-S47.

The human population is exposed to both the ultraviolet A (UVA) and B (UVB) regions of the solar spectrum. UVB induces mainly dipyrimidine photoproducts in DNA by a direct photochemical mechanism, whereas UVA is absorbed by other cellular constituents and induces mainly oxidative damage indirectly. The proportions of the different dipyrimidine photoproducts, and the ratio of dipyrimidine to oxidative damage depend on the exact spectral output of a UV source. Irradiation of human epidermal keratinocytes induces release of cytokines, with cyclobutane pyrimidine dimers playing a significant role in the process. These cytokines may then modulate the activity of cells of the immune system. Freshly isolated human lymphocytes are exquisitely sensitive to UVB irradiation, because of their low deoxyribonucleotide pools. They also have a separate defect in removal of cyclobutane pyrimidine dimers from their DNA. We have observed that frequencies of mutations at the hprt locus in human T-lymphocytes and translocations involving the bcl2 locus in B-lymphocytes appear to be associated with sunlight levels over the period before the blood sample was taken. This may be an indirect cytokinemediated effect, and may be relevant to the possible link between non-Hodgkin's lymphoma and sunlight. On the other hand, sunlight can have beneficial effects, and may protect against autoimmune diseases including type I diabetes and multiple sclerosis. J Epidemiol, 1999 ; 9 : S48-S57.

Ultraviolet (UV) radiation is a very common carcinogen in our environment. Epidemiological data on the relationship between skin cancers and ambient solar UV radiation are very limited. Hairless mice provide the possibility to study the process of UV carcinogenesis in more detail. Experiments with this animal model have yielded quantitative data on how tumor development depends on dose, time and wavelength of the UV radiation. In addition, at the molecular level the interactions between UV, specific cancer genes-like the Ras oncogene family and the p53 tumor suppressor gene, together with the role of DNA repair in this process have been addressed recently. In wildtype hairless mice mutations in the p53 gene are clearly linked to UVB but not to UVA radiation. Furthermore, the p53 alterations seem to be essential early in tumor development. However, in Xpa-deficient mice this dependency on p53 alterations appeared to be different as is the tumor type induced by UVB. Research using genetically modified hairless mice should enable us to further unravel the mechanisms of UV-induced skin cancer. J Epidemiol, 1999; 9 : S58-S65.

There is ample epidemiological evidence showing that sunlight can cause skin cancer in the human. In experimental studies, simulated sunlight or UV lamps are used for demonstrating carcinogenesis and other biological effects. Little studies, however, have been performed using natural sunlight itself. In this work, we have examined the mutagenicity of natural sunlight in Drosophila. The Drosophila wing spot test is useful to detect somatic cell mutations. Third instar larvae in petri dishes were exposed to sunlight (ultraviolet region with <290 nm wavelength cut off by a plastic cover) in the yard of Okayama University campus (north latitude: 34* 39', east longitude: 133?55'). The sunlight was mutagenic in Drosophila larvae and produced pyrimidine dimers in their DNA. In the observed mutagenicity, there was dependence on the exposure period and UV fluence. During the two-year monitoring, the highest induction of mutant spot observed was 1.98 total spots/wing on June 25, 1998, and the lowest was 0.64 on December 29, 1998, while non-exposure spontaneous spots were 0.29 and 0.32 on these days, respectively. Thus, solar radiation was mutagenic both in summer and in winter. J Epidemiol, 1999 ; 9 : S66-S71.

A retroviral vector carrying both positive (neo) and negative (herpes simplex virus thymidine kinase or HSV-tk) selection markers was constructed as a substrate for mutational assay in mammalian cells. Using a population of rat fibroblast cells carrying a single copy per cell of retroviral DNA randomly integrated in their chromosomes, we examined the cytotoxic and mutagenic activities of ultraviolet light (UV) at four wavelengths (254, 290, 300, and 320 nm). The action spectra for these activities are similar to some of the previously reported spectra for photochemical DNA modifications, erythema, cell killing, and mouse skin carcinogenesis, except at 290 and 320 nm. At 290 nm, no significant mutagenicity was observed. At 320 nm, both cytotoxic and mutagenic activities were 10 times higher than the values expected from the absorption spectrum for DNA and the action spectrum for bacterial inactivation and mutagenesis. Structural comparison of some of the HSV-tk mutants obtained after irradiation with 300 and 320 nm UV revealed partially different patterns of mutation specificity, suggesting the involvement of multiple molecular mechanisms in the genotoxicity associated with this range of UV. J Epidemiol, 1999 ; 9 : S72-S77.

In the last decades the knowledge of the effects of UV radiation on human health, especially in skin cancerogenesis, but also in immunsuppression, photoaging, eye damages, has enlarged strongly. The increasing solar UV radiation and changes in life style strengthen the necessity to identify and quantitate intrinsic biomarkers which are indicative for the individual UV susceptibility and the accumulated individual UV burden. For the risk assessment of potentially deleterious UV effects extrinsic biomarkers have to be developed and tested as personal biological UV dosimeters. One example for such a well characterized biological UV dosimeter is the DLRbiofilm which consists of spores of the bacterium Bacillus subtilis as UV sensitive target. J Epidemiol, 1999; 9 : S78-S83.

Exposure to UV is a recognised risk factor for skin cancer and it also induces immunosuppression to a variety of antigens encountered following the irradiation. The latter property has been demonstrated in rodent models of infections with the microbial agents including viruses, bacteria, protozoa and helminths. In the majority of cases the severity of the symptoms and the microbial load in the host are increased as a result of the immunomodulation. UV can also affect the pathogenesis of some natural microbial infections of human subjects, such as causing recrudescence of herpes simplex virus and contributing to the oncogenic potential of papiIlomaviruses. Sufficient data have been generated from the animal models to construct a risk assessment in humans for suppression of microbial immune responses induced by sunlight exposure. This estimation requires verification from epidemiological studies and from further work to assay modulation in human immunity to particular pathogens experienced before and after the UV radiation. J Epidemiol, 1999 ; 9 : S84-S92

Using a mouse model, we examined whether UV-B was a risk factor for malarial infection. Two mouse strains, susceptible (BALB/c) and resistant (C57BL/10) to murine malaria (Plasmodium chabaudi), were UV-preirradiated and infected with a sub-lethal dose of malaria parasite (104 and 105, respectively). Parasite growth was assayed with tail-blood smears counting parasitized red blood cells. Mice resistant to malaria were bled by heart puncture and the plasma cytokines were determined. Our results showed that UV-B irradiation worsened the malarial infection and 100% of the malaria-resistant mice strains died due to a usual infection at sub-lethal dose following UV-B irradiation. In the resistant mice strain infected with the parasite, the plasma IFN-^Q production was inhibited by UV-B irradiation and the maximum titer was about one-fifth of the non-irradiated mice. Furthermore, activation of macrophages from UV-irradiated mice also decreased compared with that of non-irradiated mice. IFN-^Q administration prevented the death of UV-B irradiated resistant mice and the cure ratio was 60%. In conclusion, UV-B increased the susceptibility of both strains of mice and impaired IFN-γ production in the malaria-resistant mice strain. J Epidemiol, 1999 ; 9 : S93-S96.

A review of the epidemiological evidence linking cataract and chronic ultraviolet B radiation (UV-B) exposure was carried out. The majority of ecological studies suggest an increased risk of cataract with residence in areas of greater ambient UV-B. Studies which have measured personal ocular exposure to UV-B have found that even low exposures, as encountered in the general populations of developed countries, confer a measurable risk of cortical cataract. There is sufficient evidence of increased risk of cortical lens opacity with ocular exposure to UV-B to warrant public health messages about simple measures to decrease exposure. J Epidemiol, 1999 ; 9 : S97-S101.

We discuss the role of sunlight, mostly ultraviolet light (UV), in the induction of nonmelanoma and melanoma skin cancer. Whilst the former seems to be correlated with accumulated exposure, the causation of melanoma is more complex, and may also involve the pattern of, and age at, exposure. The efficacy of sunscreens is debatable; while they protect against UVB wavelengths (290-320 nm), and so extend the time that may be spent in the sun before becoming sunburnt, their use may subject wearers to excessive exposure to UVA (320-400 nm) and visible light. Both epidemiological surveys and experiments with animal models suggest that UVA, and perhaps the visible, may induce melanomas. Although Japanese have a much lower incidence of skin cancer than Caucasians, the dramatic rise in skin cancer in Japanese-Americans in Hawaii exposed to high-intensity irradiation raises concerns. If the Japanese people adopt sun-seeking behavior, or should the levels of UV irradiation rise significantly through depletion of the ozone layer, then this could become an important health problem in future. J Epidemiol, 1999 ; 9 : S102-S114

Ambient solar ultraviolet radiation (UVR) has been monitored around Australia by the Australian Radiation Laboratory (ARL) and its successor ARPANSA since the mid 1980's using a network of radiometric detectors and a spectroradiometer (SRM) for spectral measurements, based in Melbourne. In a continent the size of Australia, the levels vary markedly, basically following a latitude gradient increasing towards the equator but with local geographical and weather effects also evident. ARL also conducts personal exposure studies of various population groups in collaboration with other research centres to gather information on what fraction of the ambient UVR people receive. ARL also undertakes studies on the UVR protection provided by sunscreens, clothing, hats, sunglasses and other materials in an attempt to improve UVR protection used by the public. J Epidemiol, 1999 ; 9 : S115-S122.

Most ecological studies investigating the relationship between incidence and/or mortality of skin cancer and surrogate measures of ultraviolet radiation B (UVB) have been conducted among the Caucasian population. The objective of the present study was therefore to assess the geographical correlation between ambient UVB estimates and regional mortality rates for skin cancer in Japan. The standardized mortality ratio (SMR) for malignant melanoma and other malignant neoplasms of the skin was calculated by sex, region and time-period for all deaths occurring in the period 1973-1994. The Spearman's correlation coefficient was calculated between estimated ambient UVB and regional SMRs for the two types of skin cancer. There was no geographical correlation between UVB and skin cancer mortality, except for a significantly negative correlation in malignant melanoma among males and a significantly negative correlation in other malignant neoplasms of the skin confined to unexposed anatomic sites of the body among females. The characteristic ecological relationship adds to the importance of conducting further epidemiological studies at the individual level in Japan. (165 words) J Epidemiol, 1999 ; 9 : S123-Sl28.

Cutaneous malignant melanoma occurs much less frequently among non-white populationsthan among white populations. Little is known of the descriptive epidemiology of melanomaamong Japanese. We investigated time trends of incidence of invasive cutaneous malignantmelanoma using data from the Osaka Cancer Registry (Japan) among 321 men and 313 womendiagnosed between 1964-95. Average, annual, age-standardized incidence rates per 1, 000, 000population were 2.45 (95% confidence interval (CI): 2.17-2.72) for men and 2.04 (95% Cl : 1.81-2.28) for women. The age-standardized rate ratio among men from 1964-71 as a reference wasalmost constant during the study period, whereas that among women increased up to 1.8 fold(95% CI : 1.25-2.56) in 1980-87 and seems to have reached a plateau recently. Among men, theratio for head and neck lesions decreased to 0.5 fold (95% Cl : 0.26-0.99) in 1988-95. Amongwomen, the ratio for lesions of the extremities steeply increased up to 4.7 fold (95% CI : 2.68-8.35) in 1980-87 from the reference period of 1964-71, whereas a slight increase for trunk lesionsand no increase for head and neck lesions were noted during the same period. Possibleexplanations for the subsite-specific time trends are discussed.J Epidemiol, 1999 ; 9 : S129-S135.

In order to better understand the effect of chronic sun exposure on facial skin photo-aging andto identify the factors affecting it, we planned a study in two areas in Japan, Akita andKagoshima, which correspond to the low and high sun exposure environments, respectively. Asa first step, we conducted a pilot study in the two areas, examining 195 subjects.Hyper-pigmentation and wrinkling were measured with a high-resolution digital video imaging system.As expected, people in Kagoshima had darker skin, higher visual grades of facial hyper-pigmentation, and more facial wrinkles than people in Akita, reflecting the difference of UVexposure levels in the two areas. Both the grades of hyper-pigmentation and number of wrinklesincreased in a roughly linear fashion with the advancement of age. On the other hand, the effectof gender was different in those two skin photo-aging parameters. Women had higher hyper-pigmentation grades (P=0.012) and less wrinkles (P=0.004) than men. Interestingly, post-menopausal women had higher grades of hyper-pigmentation than pre-menopausal women.Neither sun exposure index for darkness nor wrinkling showed any significant differences bymenopausal status. In this pilot study, we collected information on various factors, including life-styles. The results of detail analysis will be presented elsewhere. In the present analysis, wefound that the grade of hyper-pigmentation was not related to total hours spent outside in life butwas affected by various factors, including toe-nail zinc levels. On the other hand, the number ofwrinkles was significantly related to total hours spent outside in life.The most important risk factors of non-melanoma skin cancer are chronic sun exposure, ageand male sex. All of them are strongly related to higher levels of UV exposure. The present studyconfirmed that chronic sun exposure, age and male sex were strong risk factors of the wrinklenumber. The number of wrinkles was significantly related to total hours of sun exposure in life, increased in a roughly linear fashion with the advancement of age, and was larger in men than inwomen. In epidemiological studies of UV-related skin cancer, the number of wrinkles, which canbe easily measured with a high-resolution digital video imaging system as shown in this study, may be a good marker of total sun exposure in life. J Epidemiol, 1999; 9 : S136-S142.

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